The proposed research deals with a study of the pathogenesis of diabetes mellitus in the guinea pig. The sequence of various pathologic changes in pancreas, kidney, striated muscle, capillaries, nerve, and eye will be evaluated by electron and light microscopy. The pathologic changes encountered in specimens of human pancreas from patients with and without diabetes mellitus will be studied by similar techniques. Since the guinea pig model is of contagious etiology, studies on the very early changes in pancreatic islets and vascular stroma of islets and other organs will receive special attention. These changes will be contrasted with those encountered in chronically diabetic guinea pigs.